Factor VIII (FVIII) is a plasma glycoprotein whose deficiency or if defective causes hemophilia A. FVIII circulates as a heterodimeric protein, consisting of a Ca(II) linked light chain (LC) and a heavy chain (HC). The HC, mol wt 163 kDa, contains the A1-A2-B domains and the LC, mol wt 80 kDa, contains the A3-C1-C2 domains. We are interested in studying the domain organization of these multidomain proteins FVIII, LC and HC by differential scanning calorimetry, to characterize the domain-domain interaction and structural relationship.